Toxic interactions between lithium and non-steroidal anti-inflammatory drugs.

Affective disorder and arthritis are both common conditions, and drugs form the mainstay of treatment for both illnesses. Despite the large variety of agents used to treat both disorders, toxic interactions between psychotropic and the anti-rheumatic drugs seem uncommon. One combination that has recently attracted some attention is lithium toxicity precipitated by certain non-steroidal anti-inflammatory drugs (NSAIDs). Approximately one million people in the UK suffer from rheumatoid arthritis, and probably a further three million have osteo-arthritis, a substantial proportion of these patients requiring NSAIDs. In the USA in 1982 there were 19 million prescriptions for ibuprofen (Overview, 1986). McCreadie & Morrison (1985) found that 0-77/100000 of the population were taking lithium which gives a figure of about 40000 patients taking lithium in the UK. Thus, quite large numbers of people could be taking lithium and NSAIDs together. This review covers the current literature on lithium NSAID interaction and addresses the question as to possible underlying mechanisms. So far only five cases of lithium toxicity, secondary to the addition of a NSAID, have been reported. Three of these were from the UK, one from France and one from the USA; they occurred over a seven-year period, indicating that these instances are rather rare. There have also been several studies of the effects of NSAIDs on plasma lithium levels and lithium excretion in normal human volunteer subjects. As it is thought that NSAIDs act by inhibiting prostaglandin synthesis, we examine the possibility that prostaglandins may play a role in the excretion of the lithium ion and particularly the role prostaglandins may have in drug-induced lithium nephrotoxicity. This editorial will cover the following areas. (1) The published reports of cases where toxic interactions have been reported. (2) Human studies where volunteers stabilized on lithium have been given various NSAIDs, and both lithium levels and lithium clearance have been measured. (3) Renal function and other factors which may have affected serum lithium levels. (4) Renal function and prostaglandins. (5) The possible role of prostaglandins in psychiatric disorder. (6) Animal and in vitro studies on the effects of lithium, psychotropic drugs, and NSAIDs on prostaglandin synthesis. (7) Conclusions.